The dramatic worldwide variation in esophagal cancer incidence implicates a variety of factors in the etiology of this disease and provides the opportunity to test these factors experimentally. The intractability of the disease to conventional treatment methods underlines the importance of attempting to understand whether and how these factors may alter the course of this neoplasm. The availability of a well-established animal model for esophagel carcinogenesis makes this effort possible. This research project is designed to further examine the ability of zinc deficiency, a factor associated to this neoplasm, to enhance methylbenzylnitrosamine (MBN)-induced esophageal carcinogenesis. Zinc deficiency signficantly enhances this carcinogenic process when applied only through the end of dosing or after dosing is complete, indicating an effect during different stages of the process. Zinc deficient hyperplasia can enhance the process at three stages: (1) immediately prior to carcinogen exposure by making cells more vulnerable to MBN; (2) during or after dosing by preventing proper repair of damaged DNA; and (3) by promoting tumor growth. Previous experiments showed different patterns of DNA synthesis in three dietary groups which produced different tumor incidences. Each pattern was consistent with tumor results to a certain extent; further experimentation is required to clarify the results. Zinc deficiency may also exert its effect by altering adduct levels and persistence, particularly of the promutagenic base 06-methylguanine. A number of enzymes, including polymerases, are zinc dependent and are affected during a zinc deficiency; this may be another way in which zinc deficiency may exert an effect. An understanding of repair activity in terms of the post dosing DNA synthesis patterns of inhibition and enhancement, will clarify the importance of both of these factors. Zinc deficiency may also affect the enzymes that metabolize MBN and the microflora and inflammatory response seen in the esophagus. By further limiting the time of zinc deficiency and measuring the above factors in these diet-switched groups these experiments will clarify whether zinc deficiency exerts its enhancing effect at a critical time point or cumulatively and what the role of these factors is in this process.